In a career that has spanned more than 50 years of scientific research, Philip Marcus, professor of molecular and
cell biology, has enjoyed his share of significant results and papers regarded as 'classic'.

Philip Marcus, Board of Trustees Distinguished Professor of Molecular and Cell Biology, works in his lab in
Torrey Life Sciences. Marcus has spent about half a century researching viruses and the interferon system.

Photo by Dollie Harvey

His achievements were recognized when the University named him a Board of Trustees Distinguished Professor, the
highest honor for faculty, citing his pioneering interferon research. Marcus is also interim director of the Biotechnology
Bioservices Center; a member of the Center for Excellence in Vaccine Research; and has been chair of the Institutional
Biosafety Committee for 27 years.

It's the thrill of the chase for new knowledge about viruses and the interferon system that motivates Marcus, at
76, to don his blue lab coat, write new papers, and hint to a visitor - without revealing his secret - that his
latest work will shake some people up when published.

"I don't think it's fun to do work that a lot of other people are doing - and science should be fun," he says, quoting a
scientist he greatly admires, the late Leo Szilard. Szilard was one of the Manhattan Project designers, who abandoned physics for biology after the atomic bomb - for which he received
a patent - was dropped.

Marcus was a graduate student of Szilard's at the University of Chicago, where he received his master's degree in
microbiology in 1953. He then moved to the University of Colorado for his Ph.D., where he worked under biophysicist
Theodore T. Puck.

Marcus's first research breakthrough was a paper he wrote with Puck in 1954 for the Proceedings of the National
Academy of Science, describing a technique they developed for cloning mammalian cells - the first time this had
been done. They invented the technique after Szilard offhandedly sketched on a napkin his idea for the project,
inspiring Marcus to pursue a new method.

That method is still used. A history of somatic cell genetics written in 1995 called it a "technological revolution" that "provided
the essential basis for what rapidly became the standard methodology for cloning animal cells."

Marcus's next significant work was a demonstration of cell surface migration of proteins in the early 1960's. During
a summer course at the Cold Spring Harbor Laboratory headed by Nobel laureate James Watson, Marcus - by then a junior
faculty member at Albert Einstein College of Medicine in the Bronx - described for the first time the dynamics of
the movement of virus molecules on the surface of cells.

An "intrinsic interference test" Marcus developed at Einstein made it possible to quantitatively detect rubella virus, the cause of an epidemic in the 1960's.

Interferon has occupied much of Marcus's research since 1966. He was even introduced at one scientific symposium
as 'Mr. Interferon.'

Interferon, discovered in 1957, the year Marcus earned his Ph.D., is a protein produced by humans and other animals
that activates a cell's anti-viral response. How a virus kills a healthy cell has long been one of his interests;
how interferon stops it is another. Which virus molecules induce interferon production, and, more recently, which
molecules suppress interferon induction, are also subjects of his research.

The chills or fever often experienced during a viral infection such as the flu are caused not by the virus, but
by interferon going to work. Interferon was once touted as a "miracle drug" cure for cancer, but its workings and
effects have proved to be more complex than first thought. Interferons are now produced by genetic engineering and
used as an adjunct therapy for some types of cancer and for treating certain forms of hepatitis.

Much of Marcus's research on what makes viruses and interferon tick has been conducted together with his research
associate for 30 years, Margaret Sekellick, a UConn alumna who is now a professor-in-residence.

Marcus's laboratory in the Torrey Life Sciences Building is a center of information about viruses. The lab has developed
assays, or measures, for quantifying the properties of viruses, such as their ability to cause infection, induce
interferon, kill cells, and suppress interferon induction.

The lab is the leading proponent of the theory that double-stranded ribonucleic acid, or dsRNA, is the inducer of
interferon, Marcus says. In what he describes as a "serendipitous insight" in 1975, when he and Sekellick were studying
how vesicular stomatitis virus - a virus that causes a disease in cows - kills a cell, they began to study dsRNA
produced by a defective particle of that virus.

Working on chick embryo cells, they determined that just one molecule of dsRNA was enough to induce interferon production
in a cell. Andrew Ball, a professor of microbiology at the University of Alabama who was a colleague of Marcus and
Sekellick when the work leading to the one-molecule theory was in progress, has described the scale envisaged by
the theory: "When you compare the size of a molecule and the size of a cell, it's like a pea up against the Cathedral
of Notre Dame."

Yet strangely, while a cell would respond with incredible sensitivity to one molecule of dsRNA, cells that got two
or more molecules produced little or no interferon, Marcus noted, and no one knew why. Despite considerable skepticism
by reviewers about their one-molecule theory, a paper by Marcus and Sekellick describing it appeared in Nature in
1977.

"I think it is fair to say that the full implications of this pioneering work have yet to be fully appreciated by the scientific
community," says Ball.

One area of focus in Marcus's lab has been avian interferon. In 1994, Sekellick cloned chicken interferon for the
first time. Another former student of Marcus's, Charles Weissmann of Biogen, became the first to clone the human
interferon gene.

Over the years, Marcus's work has been funded by the NIH, the National Science Foundation, the U.S. Department of Agriculture, and Connecticut
Innovations. Recently, he and Sekellick have been working on a procedure to overcome interferon resistance by some viruses.

Marcus is in his 28th year of teaching virology, a class that used to attract a fairly stable population of 30 or
so juniors, seniors, and graduate students and has nearly doubled that enrollment this year. In 1980, he introduced
information about HIV to the class. He has also taught students about ebola and influenza, viruses they might read
about in the newspaper as well as in their class notes. And this year, he will talk about the SARS virus.

While he bridles at the question of when he will retire from teaching, Marcus did retire just over a year ago after
18 years as editor-in-chief of the Journal of Interferon and Cytokine Research (interferon is a member of the cytokine
family of proteins). During his tenure as editor, he processed more than 2,000 papers.